The Usefulness of Vitamin K-Dependent Proteins in the Diagnosis of Colorectal Carcinoma.

Colorectal cancer (CRC) is one of the most common neoplasms in developed countries, with increasing incidence and mortality, even in young people. A variety of serum markers have been associated with CRC (CEA, CA 19-9), but neither should be used as a screening tool for the diagnosis or evolution staging of CRC. The sensitivity and specificity of these markers are not as good as is required, so new ones need to be found. Matrix Gla protein and PIVKA II are involved in carcinogenesis, but few studies have evaluated their usefulness in predicting the presence and severity of CRC. Two hundred patients were divided into three groups: 80 patients were included in the control group; 80 with CRC and without hepatic metastasis were included in Group 1; 40 patients with CRC and hepatic metastasis were included in Group 2. Vitamin K-dependent proteins (VKDPs) levels in plasma were determined. Patients with CRC without methastasis (Group 1) and CRC patients with methastasis (Group 2) presented significantly higher values of CEA, CA 19-9, PIVKA II (310.05 ± 38.22 vs. 430.13 ± 122.13 vs. 20.23 ± 10.90), and ucMGP (14,300.00 ± 2387.02 vs. 13,410.52 ± 2243.16 vs. 1780.31 ± 864.70) compared to control group (Group 0). Interestingly, Group 1 presented the greatest PIVKA II values. Out of all the markers, significant differences between the histological subgroups were found only for ucMGP, but only in non-metastatic CRC. Studying the discrimination capacity between the patients with CRC vs. those without, no significant differences were found between the classical tumor markers and the VKDP AUROC curves (PIVKA II and ucMGP AUROCs = 1). For the metastatic stage, the sensitivity and specificity of the VKDPs were lower in comparison with those of CA 19-9 and CEA, respectively (PIVKA II AUROC = 0.789, ucMGP AUROC = 0.608). The serum levels of these VKDPs are significantly altered in patients with colorectal carcinoma; it is possible to find additional value of these in the early stages of the disease.

Platelet lifespan and mechanisms for clearance.

PURPOSE OF REVIEW: Activated or aged platelets are removed from circulation under (patho)physiologic conditions, the exact mechanism of platelet clearance under such conditions remains unclear and are currently being investigated. This review focuses on recent findings and controversies regarding platelet clearance and the disruption of platelet life cycle. RECENT FINDINGS: The platelet life span is determined by glycosylation of platelet surface receptors with sialic acid. Recently, it was shown that platelet activation and granule release leads to desialylation of glycans and accelerated clearance of platelets under pathological conditions. This phenomenon was demonstrated to be a main reason for thrombocytopenia being a complication in several infections and immune disorders. SUMMARY: Although we have recently gained some insight into how aged platelets are cleared from circulation, we are still not seeing the full picture. Further investigations of the platelet clearance pathways under pathophysiologic conditions are needed as well as studies to unravel the connection between platelet clearance and platelet production.

From Innate Immunity to Metabolic Disorder: A Review of the NLRP3 Inflammasome in Diabetes Mellitus.

The role of the NLRP3 inflammasome is pivotal in the pathophysiology and progression of diabetes mellitus (DM), encompassing both type 1 (T1D), or type 2 (T2D). As part of the innate immune system, NLRP3 is also responsible for the chronic inflammation triggered by hyperglycemia. In both conditions, NLRP3 facilitates the release of interleukin-1ß and interleukin-18. For T1D, NLRP3 perpetuates the autoimmune cascade, leading to the destruction of pancreatic islet cells. In T2D, its activation is associated with the presence of insulin resistance. NLRP3 activation is also instrumental for the presence of numerous complications associated with DM, microvascular and macrovascular. A considerable number of anti-diabetic drugs have demonstrated the ability to inhibit the NLRP3 inflammasome.

Platelet functional abnormalities in pediatric patients with kaposiform hemangioendothelioma/Kasabach-Merritt phenomenon.

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of infancy that is commonly associated with a life-threatening thrombocytopenic condition, Kasabach-Merritt phenomenon (KMP). Platelet CLEC-2, tumor podoplanin interaction is considered the key mechanism of platelet clearance in these patients. Here, we aimed to assess platelet functionality in such patients. Three groups of 6 to 9 children were enrolled: group A with KHE/KMP without hematologic response (HR) to therapy; group B with KHE/KMP with HR; and group C with healthy children. Platelet functionality was assessed by continuous and end point flow cytometry, low-angle light scattering analysis (LaSca), fluorescent microscopy of blood smears, and ex vivo thrombi formation. Platelet integrin activation in response to a combination of CRP (GPVI agonist) and TRAP-6 (PAR1 agonist), as well as calcium mobilization and integrin activation in response to CRP or rhodocytin (CLEC-2 agonist) alone, were significantly diminished in groups A and B. At the same time, platelet responses to ADP with or without TRAP-6 were unaltered. Thrombi formation from collagen in parallel plate flow chambers was also noticeably decreased in groups A and B. In silico analysis of these results predicted diminished amounts of CLEC-2 on the platelet surface of patients, which was further confirmed by immunofluorescence microscopy and flow cytometry. In addition, we also noted a decrease in GPVI levels on platelets from group A. In KHE/KMP, platelet responses induced by CLEC-2 or GPVI activation are impaired because of the diminished number of receptors on the platelet surface. This impairment correlates with the severity of the disease and resolves as the patient recovers.

Activated Hepatic Stellate Cells (Ito Cells) - Marker of Advanced Fibrosis in Chronic Viral Hepatitis C: A Pilot Study.

BACKGROUND AND AIMS: The aim of this study is to determine whether activated hepatic stellate cells (HSCs) may represent a prognostic marker of progressive liver fibrosis in chronic viral hepatitis C (VHC) before antiviral therapy. The possible correlation between HSCs immunohistochemical features, histopathological aspects and clinical data before therapy were also studied. METHODS: This retrospective pilot study was conducted on 27 liver biopsies from VHC patients before antiviral therapy. HSCs's immunohistochemical analysis used the antibodies alpha-smooth muscle actin (α-SMA), glial fibrillary acidic protein (GFAP) and vinculin. We correlated immunopositive HSCs with HCV load, liver stiffness (LS), fibrosis stage and necro-inflammatory degree before treatment. Also, we assessed the association between liver fibrosis after therapy, the sustained virological response at 12 weeks after therapy (SVR 12) and the type of therapy. RESULTS: HSCs were increased in VHC patients compared to controls, mainly in the intermediate and periportal lobular regions. α-SMA and vinculin HSCs correlated positively with fibrosis stage (p=0.044), (p=0.028). Furthermore, α-SMA and vinculin HSCs were associated with LS (p=0.027), (p=0.002) and viral load (p=0.021), (p=0.006), but not with necro-inflammation degree. GFAP HSCs inversely correlated with fibrosis stage (r= -0.475), LS (r= -0.422) and HCV load (r= -0.517), but positively with necro-inflammation degree (p=0.038). Liver fibrosis post therapy correlated positively with SVR12 (p<0.001) and the type of therapy (p=0.006) and SVR12 correlated positively with treatment's type (p=0.002). CONCLUSIONS: Activated HSCs may represent a marker of increased liver fibrosis in VHC. Different immunohistochemical markers can detect various HSCs subpopulations involved in the evolution of VHC and liver fibrosis.

Bioactive Compounds in Moringa oleifera: Mechanisms of Action, Focus on Their Anti-Inflammatory Properties.

Moringa oleifera (M. oleifera) is a tropical tree native to Pakistan, India, Bangladesh, and Afghanistan; it is cultivated for its nutritious leaves, pods, and seeds. This scientific study was conducted to outline the anti-inflammatory properties and mechanisms of action of bioactive compounds from M. oleifera. The existing research has found that the plant is used in traditional medicine due to its bioactive compounds, including phytochemicals: flavonoids and polyphenols. The compounds are thought to exert their anti-inflammatory effects due to: (1) inhibition of pro-inflammatory enzymes: quercetin and kaempferol inhibit the pro-inflammatory enzymes (cyclooxygenase and lipoxygenase); (2) regulation of cytokine production: isothiocyanates modulate signaling pathways involved in inflammation, such as the nuclear factor-kappa B (NF-kappa B) pathway; isothiocyanates inhibit the production of pro-inflammatory cytokines such as TNF-α (tumor necrosis factor α) and IL-1ß (interleukin-1ß); and (3) antioxidant activity: M. oleifera contains flavonoids, polyphenols, known to reduce oxidative stress and inflammation. The review includes M. oleifera's effects on cardiovascular protection, anti-hypertensive activities, type 2 diabetes, inflammatory bowel disease, and non-alcoholic fatty liver disease (NAFLD). This research could prove valuable for exploring the pharmacological potential of M. oleifera and contributing to the prospects of developing effective medicines for the benefit of human health.

Change in Neuroticism and Extraversion among Pre-University Education Employees during the COVID-19 Pandemic.

Background and objectives: Since the first reports of SARS-CoV-2 infection cases in China, the virus has rapidly spread to many countries, including Romania. In Romania, schools were closed in March 2020 to prevent the virus from spreading; since then, they have been sporadically opened, but only for a short time. Teachers had to adopt online education methods, experiencing real difficulties in their attempts to maintain high-quality teaching, as a result of social distancing from students and colleagues. The current study aimed to evaluate the burden on the neuroticism states of employees in the pre-university education system during the COVID-19 pandemic. Materials and Methods: A prospective study was conducted, in which personality trait data from 138 employees were collected via a questionnaire (EPI, Eysenck Personality Inventory), which measured extraversion-introversion and neuroticism scores before and during the COVID-19 pandemic. Initially, 150 subjects were invited to participate in the study, although 12 of them refused to participate. Based on the questionnaire not being fully filled in a further three subjects were excluded from the study, leaving a total of 135, of which 115 were woman and 20 were men. Results: The results demonstrate that the subjects included in the study expressed higher neuroticism during the COVID-19 pandemic than in the pre-pandemic period. This change could promote more stress and depression symptoms. Subjects with high school education had significantly lower neuroticism scores over time than those with university education (p = 0.006). Furthermore, we found extraversion scores to be statistically significant in our population (p = 0.022). Conclusion: The gender and living environment of the teachers were not significantly associated with the reduction in the extraversion score, but were more frequently found among older persons and in subjects without higher education. Subjects of Hungarian ethnicity had lower extraversion scores than those of Romanian ethnicity.

Longitudinal multiparametric characterization of platelet dysfunction in COVID-19: Effects of disease severity, anticoagulation therapy and inflammatory status.

INTRODUCTION: Defects of platelet functional responses in COVID-19 were reported, but their origin and pathophysiological significance are unclear. The objective of this study was to characterize the thrombocytopathy in COVID-19. MATERIALS AND METHODS: Analysis of platelet functional responses to activation by flow cytometry and aggregometry in 46 patients with confirmed COVID-19 of different severity (non-ICU, ICU, and ECMO) over the course of hospitalization alongside with plasma coagulation, inflammatory markers (CRP, fibrinogen, NETosis assays in smears) was performed. RESULTS AND CONCLUSIONS: All patients had increased baseline percentage of procoagulant platelets (healthy: 0.9 ± 0.5%; COVID-19: 1.7 ± 0.6%). Patients had decreased agonist-induced platelet GPIb shedding (1.8 ± 0.7 vs 1.25 ± 0.4), P-Selectin exposure (1.51 ± 0.21 vs 1.1 ± 0.3) and aggregation. The values of these parameters among the non-ICU and ICU cohorts differed modestly, while the ECMO cohort differed significantly. Only ECMO patients had pronounced thrombocytopenia. While inflammatory markers improved over time, the observed platelet functional responses changed only moderately. SARS-CoV-2 RNA was found in 8% of blood samples and it did not correlate with platelet counts or responses. All patients had increased NETosis that moderately correlated with platelet dysfunction. High cumulative dosages of LMWH (average > 12,000 IU/day over 5 days) resulted in an improvement in platelet parameters. The observed pattern of platelet refractoriness was reproduced by in vitro pre-treatment of washed platelets with subnanomolar thrombin or perfusion of blood through a collagen-covered flow chamber. We conclude that platelet dysfunction in COVID-19 is consistent with the intravascular-coagulation-induced refractoriness rather than with an inflammation-induced mechanism or a direct activation by the virus.

Comparative assessment of health-related quality of life with and without anticonvulsant therapy in patients with childhood epilepsy with centrotemporal spikes.

OBJECTIVE: To estimate anti-seizure medication (ASM) treatment burden and its effects on health-related quality of life (HRQOL) in new-onset childhood epilepsy with centrotemporal spikes (CECTS) using different treatment approaches in Kazakhstan. METHODS: Forty-three patients were followed prospectively during 2015 to 2020 for at least 2 years. Patients were divided into three groups: (1) history of ≤3 seizures (n = 32); (2) ≥4 seizures (n = 6); (3) cerebral palsy coexisting with CECTS (n = 5). The first group was subdivided into treated (n = 8) and observed (n = 24) subgroups. The shortened Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) was completed by parents after 6 months of follow-up. RESULTS: At the end of the study, all children had a sustained remission from seizures for at least 2 years. Differences were identified in emotional, social, and physical subscales between patients in the low seizure frequency group. Signs of low self-esteem, anxiety, depression, limited social interaction owing to pharmacotherapy, painful medical procedures, and stigma were reasons for decreased HRQOL in the treated subgroup. Overall HRQOL in treated (89.2 ± 5.2) patients was significantly decreased compared with observed children with low seizure frequency (98.0 ± 3.0). CONCLUSION: ASM therapy does not necessarily improve and may decrease HRQOL in children with low seizure frequency CECTS.

A Self-Limited Childhood Epilepsy as Co-Incidental in Cerebral Palsy.

BACKGROUND: Cerebral palsy is the most frequent motor disability in childhood and is associated with a higher incidence of seizure disorders. In many instances, it is recognized that motor difficulties, as well as seizures, are from the same underlying brain lesion. However, self-limited childhood epilepsies, being a common group of epilepsy syndromes, would be expected to occur in patients with cerebral palsy merely on chance association and be unrelated to the structural brain imaging abnormality causing the motor impairment. Differential diagnosis in this case is important determining the long-term prognosis and need for anticonvulsant treatment. CASE PRESENTATION: Here, we report two patients with cerebral palsy combined with epilepsy, whose age at onset, seizure semiology and electroclinical features were similar to children with self-limited childhood-specific seizure disorders (childhood epilepsy with centrotemporal spikes and Panayiotopoulos syndrome). CONCLUSION: These cases highlight the importance of comprehensive differential diagnosis of seizures in cerebral palsy. Co-existence of age-dependent focal epilepsies with an underlying brain pathology as white matter injury, not affecting the cerebral cortex, might take place in the case of children with impaired motor skills. With health systems increasingly utilizing clinical pathways, it is important to consider the possibility of a self-limited childhood epilepsy and avoid aggressive and unnecessary medication treatment in children with cerebral palsy.

Assessment of subclinical diabetic cardiomyopathy by speckle-tracking imaging.

BACKGROUND: Diastolic dysfunction is traditionally believed to be the first subclinical manifestation of diabetic cardiomyopathy (DCM), leading to systolic dysfunction and then overt heart failure. However, in the last few years, several studies suggested that systolic subclinical dysfunction measured by speckle-tracking echocardiography (STE) may appear ahead of diastolic dysfunction. In this review, the main endpoint is to show whether subclinical myocardial systolic dysfunction appears ahead of diastolic dysfunction and the implication this may have on the evolution and management of DCM. MATERIALS AND METHODS: We performed a search in PubMed for all relevant publications on the assessment of DCM by STE from 1 June 2015 to 1 June 2020. RESULTS AND CONCLUSIONS: The results illustrate that subclinical systolic dysfunction assessed by STE is present in early DCM stages, with or without the association of diastolic dysfunction. This could be a promising perspective for the early management of patients with DCM leading to the prevention of the overt form of disease.

The Impact of Obesity on Left Ventricular Hypertrophy and Diastolic Function in Caucasian Children.

Background: Left ventricular hypertrophy (LVH) and diastolic dysfunction are correlated with obesity and hypertension in adult patients, but few studies have investigated the association between obesity itself and left ventricular function in children. The aim of this study was to evaluate the effect of obesity and LVH on left ventricular diastolic function in pediatric subjects compared with children without obesity. Methods: A number of 454 patients from an outpatient cardiology service were enrolled in a prospective study, 33 children with obesity, 20 overweight children, and 401 children without obesity. The subjects were assigned to three groups according to age and school grade. A standardized two-dimensional echocardiography analysis was performed in all children. The evaluated echocardiographic parameters included thickness of the interventricular septum (IVS), thickness of the posterior wall of the left ventricle, and left atrium size. The left ventricular diastolic function was analyzed by the classic pulsed-wave Doppler technique, tissue Doppler technique, and continuous Doppler technique. Results: The number of children with obesity was higher in the school and adolescent groups. The median age of children with obesity was 9 years. The subjects were classified according to blood pressure values in hypertensive, with high-normal blood pressure/prehypertension and with normal blood pressure values. Standard echocardiography showed that children with obesity had significantly increased thickness of the IVS and of the posterior wall compared with nonobesity subjects (P < 0.001). Left ventricular systolic function was preserved in both groups. Diastolic function was normal in the obesity group and in the non-obesity group, respectively. Conclusions: The results of this study demonstrate that childhood obesity is associated with significant changes in the myocardial structure consisting of LVH, but we did not find an early alteration in the left ventricular diastolic function of the subjects with obesity compared with patients with a normal weight.

Cardiovascular Risk Factors and Physical Activity for the Prevention of Cardiovascular Diseases in the Elderly.

Cardiovascular diseases create an important burden on the public health systems, especially in the elderly, mostly because this group of patients frequently suffer from multiple comorbidities. Accumulating cardiovascular risk factors during their lifetime has a detrimental effect on an older adult's health status. The modifiable and non-modifiable cardiovascular risk factors are very diverse, and are frequently in a close relationship with the metabolic comorbidities of the elderly, mainly obesity and Diabetes Mellitus. In this review, we aim to present the most important cardiovascular risk factors which link aging and cardiovascular diseases, starting from the pathophysiological links between these factors and the aging process. Next, we will further review the main interconnections between obesity and Diabetes Mellitus and cardiovascular diseases of the elderly. Lastly, we consider the most important aspects related to prevention through lifestyle changes and physical activity on the occurrence of cardiovascular diseases in the elderly.